Kerboeuf D, Guégnard F, Vern Y Le
UR-086, MultiResistances and Antiparasitic drugs, INRA, 37380 Nouzilly, France.
Parasitol Res. 2003 Sep;91(1):79-85. doi: 10.1007/s00436-003-0942-2. Epub 2003 Jul 29.
The "multidrug resistance" (MDR) system involves the action of transmembrane P-glycoproteins (Pgp) which may be responsible for failure of chemotherapy in both invertebrates and vertebrates. We previously obtained partial reversion of anthelmintic resistance in nematodes subjected to both anthelmintics and inhibitors of this system. The results presented here are able to describe more accurately the presence of Pgp in nematodes because of the use of C219 and UIC2 monoclonal antibodies, which are used for the detection of human and mouse mdr1 gene products. These antibodies demonstrated the presence of Pgp in eggshells. Their role in these structures, which are considered to be passive barriers, remains to be determined. Flow cytometry analyses of the UIC2 staining allowed determination of the resistance of individuals, which varied within the parasite population. UIC2 demonstrated both the presence and activity of Pgp in nematodes as has previously been shown in tumour cells. Resistance seems to be due to an increase in both the number of Pgp sites and parasites with high levels of Pgp.
“多药耐药”(MDR)系统涉及跨膜P-糖蛋白(Pgp)的作用,这可能是导致无脊椎动物和脊椎动物化疗失败的原因。我们之前发现,对线虫同时使用驱虫药和该系统的抑制剂,可使驱虫抗性部分逆转。由于使用了C219和UIC2单克隆抗体(用于检测人类和小鼠mdr1基因产物),此处呈现的结果能够更准确地描述线虫中Pgp的存在情况。这些抗体证实了Pgp存在于卵壳中。它们在这些被视为被动屏障的结构中的作用仍有待确定。对UIC2染色进行的流式细胞术分析能够确定个体的抗性,抗性在寄生虫群体中存在差异。UIC2证实了线虫中Pgp的存在及活性,这与之前在肿瘤细胞中的情况一致。抗性似乎是由于Pgp位点数量增加以及Pgp水平高的寄生虫数量增多所致。